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Patients with relapsed/refractory multiple myeloma (RRMM) resistant to multiple drug classes remain a high unmet need population. This longitudinal retrospective cohort study assessed real-world treatment patterns and outcomes in adults with RRMM. Patients who had three or more prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (double-exposed) were further categorized as refractory to a PI and an immunomodulatory agent (double-class refractory

Azithromycin is a common first-line antibiotic for respiratory infection; however, there is conflicting evidence regarding risk of cardiovascular death. We assessed cardiovascular and noncardiovascular mortality associated with azithromycin versus amoxicillin-clavulanate among US Veterans treated for nonear-nose-throat respiratory infection ("respiratory") or ear-nose-throat infection indication.Electronic health record data from the US Veterans Health Administration database were used to identify Veterans (30-74 years) with outpatient dispensings of oral azithromycin versus amoxicillin-clavulanate for respiratory or ear-nose-throat infection (January 01, 2000-December 31, 2014). Outcomes assessed were risk of cardiovascular death and noncardiovascular death within 1-5 and 6-10 days postdispensing. Inverse probability of treatment-weighted proportional hazards models and binomial regression models were used to estimate hazard ratios (HRs) and compute risk differences (RD) per million courses of therapy. Cardiac death (subset of cardiovascular death) was assessed in sensitivity analyses.There were 629 345 azithromycin and 168 429 amoxicillin-clavulanate dispensings for respiratory indications, 143 783 azithromycin, and 203 142 amoxicillin-clavulanate dispensings for ear-nose-throat indications. For respiratory indications, azithromycin was not associated with a significantly different risk of cardiovascular death versus amoxicillin-clavulanate within 1-5 days postdispensing (HR [95% confidence interval (CI)]: 1.12 [0.63, 2.00]; RD [95% CI]: 11 [-43, 64] deaths/million courses of therapy). No elevated risk for azithromycin was found for ear-nose-throat indications. Pooled results for both indications via meta-analysis showed no association between antibiotics and cardiovascular mortality. There was no significant difference in risk of noncardiovascular or cardiac death between antibiotics postdispensing.Azithromycin was not associated with elevated risk of cardiovascular or noncardiovascular death versus amoxicillin-clavulanate among US Veterans.

To obtain a nationally representative annualized estimate of the prevalence of pericarditis (inflammation of the pericardium) in the United States (US) in order to better understand the potential burden on the health care system. Three nationally representative datasets were used to estimate the annualized period prevalence and prevalence rate of pericarditis from 2007 to 2016: the National Ambulatory Medical Care Survey (NAMCS), the National Hospital Ambulatory Medical Care Survey (NHAMCS), and the Nationwide Inpatient Sample (NIS). Across all data sources, ICD-9/10 codes were used to identify healthcare encounters with ≥1 primary or secondary diagnosis related to pericarditis irrespective of duration or etiology. The prevalence of pericarditis in 2020 was extrapolated by multiplying the average annualized prevalence rate from 2007 to 2016 by the total US population as of March 2020. Data from NAMCS/NHAMCS (2007–2016) yielded an average annualized estimate of 125,209 patients with pericarditis, resulting in a pooled average annualized prevalence estimate of 40 patients with pericarditis per 100,000 persons. Data from NIS (2007–2016) yielded an average annualized estimate of 34,441 patients with pericarditis, resulting in a pooled average annualized prevalence estimate of 11 hospitalized patients with pericarditis per 100,000 persons. Extrapolation of these results based on the March 2020 population estimates from the US Census Bureau of 329,436,928 resulted in an estimated US prevalence of pericarditis to be approximately160,000. Despite certain methodologic limitations, our analysis of data from nationally representative sources support that pericarditis is a rare disease affecting substantially fewer than 200,000 persons in the US.

Novel agents, including Bruton tyrosine kinase inhibitors (BTKis), have become the standard of care for patients with chronic lymphocytic leukemia (CLL). We conducted a real-world retrospective analysis of CLL patients treated with acalabrutinib vs ibrutinib to compare outcomes utilizing the Flatiron Health Database. Patients with CLL were included if they initiated acalabrutinib or ibrutinib between 1/1/2018-2/28/2021. The primary outcome of interest was time to treatment discontinuation (TTD). Average treatment effect among the treated weighting was used to balance key baseline characteristics between cohorts. Kaplan-Meier analysis was used to estimate unweighted and weighted median TTD. A weighted Cox proportional-hazards model was used to compare TTD between cohorts. Out of 2509 patients included in the analysis, 89.6% received ibrutinib and 14.1% received acalabrutinib. TTD was not significantly different between cohorts in the unweighted analysis. After weighting, the cohorts were balanced on all baseline characteristics except cardiovascular risk factors and baseline medications use. The median (95% CI) TTD was not reached (NR; 25.1, NR) for the acalabrutinib cohort and was 23.4 months (18.1, 28.7) for the ibrutinib cohort. The discontinuation rate at 12 months was 22% for the weighted acalabrutinib cohort vs 31% for the weighted ibrutinib cohort (P = .005). After additional adjustments for prior BTKi use, the acalabrutinib cohort had a 41% lower risk of discontinuation vs. ibrutinib (HR 0.59; 0.43, 0.81; P = .001). In the largest available study comparing two BTKis, patients with CLL receiving acalabrutinib demonstrated lower rates of discontinuation and a prolonged time to discontinuation vs ibrutinib.

Supplementary Data from Real-World Evidence in Support of Oncology Product Registration: A Systematic Review of New Drug Application and Biologics License Application Approvals from 2015–2020

Real-world evidence (RWE) has garnered great interest to support registration of new therapies and label expansions by the United States Food and Drug Administration (FDA). Currently, practical insights on the design and analysis of regulatory-grade RWE are lacking. This study aimed to analyze attributes of real-world studies in FDA's decision-making and characteristics of full versus accelerated approvals through a systematic review of oncology product approvals. Oncology approvals from 2015 to 2020 were reviewed from FDA.gov. Applications were screened for inclusion of RWE, and variables related to regulatory designations of the application, pivotal clinical trial, and real-world studies were extracted. FDA feedback was reviewed to identify takeaways and best practices for adequate RWE. Among 133 original and 573 supplemental approvals for oncology, 11 and 2, respectively, included RWE; none predated 2017. All real-world studies were retrospective in nature; the most common data source was chart review, and the most common primary endpoint was overall response rate, as in the pivotal trial. The FDA critiqued the lack of the following: a prespecified study protocol, inclusion/exclusion criteria matching to the trial, comparability of endpoint definitions, methods to minimize confounding and address unmeasured confounding, and plans to handle missing data. All full (versus accelerated) approvals shared the following characteristics: high magnitude of efficacy in the pivotal trial; designations of orphan disease, breakthrough therapy, and priority review; and no advisory committee meeting held. This study found that findings from external control real-world studies complemented efficacy data from single-arm trials in successful oncology product approvals.

To compare treatment patterns of United States (US) veterans stable on innovator infliximab (IFX) who switched to an IFX biosimilar (switchers) or remained on innovator IFX (continuers).US Veterans Healthcare Administration data (01/2012-12/2019) were used to identify adults with rheumatoid arthritis (RA), psoriatic arthritis (PsA), plaque psoriasis (PsO), ankylosing spondylitis (AS), or Crohn's disease and ulcerative colitis (i.e. inflammatory bowel disease [IBD]), treated with innovator or biosimilar IFX. Index date was the first IFX biosimilar administration for switchers or a random innovator IFX administration for continuers. Patients were required to have ≥5 innovator IFX administrations during the 12 months pre-index (prevalent population). Patients with ≥12 months of observation prior to the first innovator IFX administration were analyzed as the primary population (incident population), and data were assessed from start of innovator IFX. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. Treatment patterns were evaluated post-index; continuers were censored before switching to IFX biosimilar. Discontinuation was defined as switching to another biologic (including innovator IFX) or having ≥120 days between 2 consecutive index treatment records.In the incident population, mean [median] duration of follow-up was 737 [796] days among switchers (Patients switching from innovator to biosimilar IFX were more likely to discontinue treatment and switch to another innovator biologic (notably back to innovator IFX) than those remaining on innovator IFX; however, reasons for discontinuation and switching are unknown.

Real-world evidence (RWE) has garnered great interest to support registration of new therapies and label expansions by the United States Food and Drug Administration (FDA). Currently, practical insights on the design and analysis of regulatory-grade RWE are lacking. This study aimed to analyze attributes of real-world studies in FDA's decision-making and characteristics of full versus accelerated approvals through a systematic review of oncology product approvals. Oncology approvals from 2015 to 2020 were reviewed from FDA.gov. Applications were screened for inclusion of RWE, and variables related to regulatory designations of the application, pivotal clinical trial, and real-world studies were extracted. FDA feedback was reviewed to identify takeaways and best practices for adequate RWE. Among 133 original and 573 supplemental approvals for oncology, 11 and 2, respectively, included RWE; none predated 2017. All real-world studies were retrospective in nature; the most common data source was chart review, and the most common primary endpoint was overall response rate, as in the pivotal trial. The FDA critiqued the lack of the following: a prespecified study protocol, inclusion/exclusion criteria matching to the trial, comparability of endpoint definitions, methods to minimize confounding and address unmeasured confounding, and plans to handle missing data. All full (versus accelerated) approvals shared the following characteristics: high magnitude of efficacy in the pivotal trial; designations of orphan disease, breakthrough therapy, and priority review; and no advisory committee meeting held. This study found that findings from external control real-world studies complemented efficacy data from single-arm trials in successful oncology product approvals.

Cardiac resynchronization therapy (CRT) can improve cardiac function in patients with heart failure (HF); however, in some patients, HF worsens despite CRT. This study characterized the long-term clinical burden of patients with and without HF worsening (HFW) within 6 months post CRT implantation. A claims database (2007–2018) was used to identify two cohorts of adults: those with HFW within 180 days post-CRT and those with no HFW (NHFW). The evaluated clinical outcomes were cardiovascular events/complications, HF-related interventions, hospice enrollment, and all-cause mortality. Inverse probability of treatment weighting (IPTW) was used to adjust for confounders; adjusted comparisons were assessed using weighted Cox proportional hazard ratios (HRs). Among the 12,753 adults analyzed (HFW: N = 4,785; NHFW: N = 7,968), the mean age was 72 years and the mean duration of follow-up was approximately 2 years. The clinical burden was greater for HFW than for NHFW in terms of all-cause mortality (19.7% vs. 12.1%) and occurrence of atrial fibrillation (57.4% vs. 51.2%). In the IPTW-adjusted Cox proportional hazard analyses, patients with HFW had a 54% higher average hazard of experiencing all-cause mortality compared to NHFW (adjusted average HR = 1.54, 95% confidence interval [CI]: 1.41–1.70; p < .001). Of the clinical events experienced by ≥5% of patients, the greatest differences in average hazard were for HF decompensation (adjusted average HR = 1.83, 95% CI: 1.60–2.09) and HF decompensation or death (HR = 1.63, 95%CI: 1.50–1.77). Patients with early HFW post-CRT experienced a significantly higher clinical burden than those without HFW. Vigilance for signs of worsening HF in the first 6 months post-CRT is warranted.

Introduction:Limited real-world data are available on treatment sequences for patients with metastatic hormone-sensitive prostate cancer treated with androgen deprivation therapy plus docet...

Although cardiac resynchronization therapy (CRT) has the potential to improve cardiac function in patients with heart failure (HF), a considerable portion of patients do not respond to therapy. This study assessed the economic burden among patients with and without HF worsening after receiving CRT in real-world practice. In this retrospective claims-based study using Optum’s de-identified Clinformatics® Data Mart Database (January 2007–December 2018), adults who received CRT were stratified into two cohorts based on whether they showed evidence of HF worsening within 180 days post-CRT implantation. Inverse probability of treatment weighting (IPTW) was used to adjust for confounding, accounting for demographics (e.g., age, sex), the Quan–Charlson Comorbidity Index, other clinical characteristics, healthcare resource utilization (HRU), and healthcare costs during the 180 days pre-CRT (baseline period). Annualized all-cause and congestive HF-related HRU and healthcare costs from payer and patient perspectives were assessed from day 181 post-CRT (follow-up period), and compared between cohorts using incidence rate ratios (IRRs) and cost ratios (CRs). This study included 12,753 patients (n = 4785 with HF worsening; n = 7968 without). Mean age was 72 years and roughly two-thirds were male. Baseline characteristics were balanced between cohorts post-IPTW. During follow-up, patients with HF worsening had significantly greater annual all-cause inpatient [adjusted IRR (95% confidence interval) = 1.55 (1.44, 1.66), p

Background: Limited information is available about treatments and clinical outcomes among men with metastatic castration-resistant prostate cancer (mCRPC) whose tumors harbor DNA damage repair (DDR) mutations. Methods: This retrospective chart review study included men diagnosed with mCRPC with ≥1 DDR mutation detected by tumor comprehensive genomic profiling who began a line of therapy on or after July 1, 2014, at oncology centers in the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) consortium. The index date was the initiation of a new therapy in this period, in patients who developed castration-resistant disease and progressed while receiving androgen deprivation therapy. Data on all available lines of therapy post-index were collected. Outcomes reported include time to treatment discontinuation for any reason (TTTD) and overall survival (OS), which were assessed using Kaplan-Meier analyses. Results for tumor response-related endpoints are forthcoming. Results: A total of 138 patients with mCRPC met the inclusion criteria. The mean age at index was 68 years, and 76% of patients were White. The median follow-up time was 27.1, 15.9, 11.3, and 9.4 months for 1L, 2L, 3L, and 4L+ therapy, respectively. Common sites of metastases included bone (74%), lymph nodes (69%), and lungs (10%). Common tumor DDR mutations included CDK12 (48%), BRCA2 (23%), ATM (21%), and BRCA1 (8%). Assessment of germline mutations was conducted in 114 (83%) patients; the most common was BRCA2 (8%). First-line (1L) treatment information was available for 119 (86%) patients, 2L for 101 (73%), and 3L for 75 (54%) patients. Novel hormonal therapy (NHT; 55%) and taxane chemotherapy (20%) were most common in 1L. Enzalutamide (35%) and abiraterone acetate (14%) were the most frequently used NHTs. Compared to 1L, the proportion of patients receiving NHTs was lower in 2L (33%) and 3L (17%), while the proportion of patients receiving taxanes was higher (36% in 2L and 31% in 3L). In 3L, poly ADP-ribose polymerase (PARP) inhibitors were used in 21% of patients. Median TTTD was 5.6 months (95% CI: 4.2, 7.2) in 1L, 3.9 months (95% CI: 3.0, 4.6) in 2L, and 4.0 months (95% CI: 3.3, 4.7) in 3L. Median OS was 36.3 months (95% CI: 30.7, 47.8) from the start of 1L, 21.1 months (95% CI: 15.6, 29.3) from the start of 2L, and 14.1 months (95% CI: 9.5, 20.5) from the start of 3L. Conclusions: These findings provide real-world insights about treatment patterns and clinical outcomes among patients with mCRPC harboring DDR mutations. Such insight may provide a helpful benchmark for research aimed at improving clinical outcomes, particularly in later lines of therapy. Citation Format: David B. Solit, Niharika B. Mettu, Shannon J. McCall, Mallika Dhawan, Priyanka J. Bobbili, Maral DerSarkissian, Jasmina Ivanova, Bhakti Arondekar, Jane Chang, Alexander Niyazov, Jocelyn Lee, Risha Huq, Michelle Green, Michelle Turski, Aruna Muthukumar, Tracy Guo, Mei Sheng Duh, William K. Oh. Treatment patterns and overall survival among men with metastatic castration-resistant prostate cancer harboring DDR mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 930.

Background: Limited information is available about real-world treatment patterns and survival among patients with metastatic breast cancer (mBC) with BRCA1/2 mutations. BRCA1/2 mutations, which are involved in the repair of DNA double-strand breaks, are rare. Since 2018, PARP inhibitors (olaparib and talazoparib) have been approved for the treatment of patients with germline BRCA-mutated HER2-negative locally advanced and/or mBC. Methods: This retrospective chart review study included adults diagnosed with mBC with ≥1 oncogenic somatic BRCA1/2 mutation detected by tumor comprehensive genomic profiling who began a line of therapy on or after July 1, 2014, at 3 oncology centers in the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) consortium. The index date was the first initiation of a new therapy for mBC in this period (which could be first-line [1L] or subsequent line of therapy). Data on all available lines of therapy post-index were collected. Treatments received in different lines of therapy for mBC and overall survival (OS) were described separately for patients with HR-positive/HER2-negative (HR+/HER2-) mBC, triple negative mBC (TNBC), and HER2-positive (HER2+) mBC. OS from the start of each line of therapy was assessed using Kaplan-Meier analysis. Results: A total of 48 women with mBC met the inclusion criteria. The mean age at index was 58 years; 73% of women were White. Common sites of metastases included lymph nodes (56%), bone (52%), and lungs (31%). Somatic BRCA1 mutation was detected in 48% and BRCA2 mutation was detected in 54% of women. Assessment of germline BRCA mutations was conducted in 25 (52%) women; 2 (8%) of assessed women tested positive for germline BRCA mutations. 29 (60%) of women had HR+/HER2- mBC, 9 (19%) had TNBC, 9 (19%) had HER2+ mBC, and 1 woman had unknown HER2 status. Treatments received in different lines of therapy for mBC and OS from start of each line of therapy by HR and HER2 status are reported in Table 1. Common treatments for women with HR+/HER2- mBC included endocrine-based therapy, and chemotherapy. Women with TNBC were most often treated with chemotherapy. Women with HER2+ mBC most often received endocrine-based therapy in 1L; chemotherapy or HER2-targeted combination therapy in second-line (2L); and chemotherapy or HER2-targeted monotherapy in third-line (3L). Median OS from the start of 1L therapy was 37.5 months among women with HR+/HER2- disease; 20.0 months for women with TNBC; and 51.7 months for women with HER2+ disease. Conclusions: These findings provide real-world insights about treatment patterns and survival among women with mBC and BRCA1/2 mutations. Further studies with larger sample sizes are needed to confirm these findings. Table 1. Treatment patterns and survival by line of therapy, HR, and HER2 status among patients with BRCA1/2 mutated mBC Citation Format: Priyanka Bobbili, Jasmina Ivanova, David B. Solit, Niharika Mettu, Shannon McCall, Mallika Dhawan, Maral DerSarkissian, Bhakti Arondekar, Jane Chang, Alexander Niyazov, Jocelyn Lee, Risha J. Huq, Michelle Green, Michelle Turski, Aruna Muthukumar, Mianzhao Guo, Mei Sheng Duh, William Oh. Real-world treatment patterns and survival among adults with metastatic breast cancer with BRCA1/2 mutations [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-30.

29 Background: Prostate cancer (PC) disproportionately affects Black or African American (BAA) men in the United States (US), but racial disparities in outcomes are not well understood. This study analyzed racial disparities in OS, healthcare resource utilization (HRU), and PC treatments in Medicaid-insured metastatic castration resistant PC (mCRPC) patients. Methods: This retrospective longitudinal cohort study evaluated de-identified data from the Centers for Medicare and Medicaid Services 100% Medicaid data files from 01/01/2010 – 12/31/2018. The study included adult patients with a diagnosis of PC and metastasis, and a claim for at least one of the following drugs prior to 9/30/2018, which is specific to mCRPC (date defined index): ≥1 claim for cabazitaxel, mitoxantrone, enzalutamide, radium-223, or sipuleucel-T, ≥1 claim for abiraterone acetate before June 2017, ≥1 claim for docetaxel at least 90 days after initiation of hormone therapy, or evidence of castration resistance. Patients were required to be continuously enrolled for ≥6 months pre-index (i.e., baseline period) and ≥3 months post-index. Outcomes were assessed from the index date to the earliest of end of continuous enrollment, data availability, or death. A multivariable Cox proportional hazards model of OS, and a multivariable Poisson model of HRU were implemented and controlled for age, plan type, region, median state income, residence in a state with Medicaid expansion, index year, Charlson comorbidity index, baseline HRU, baseline PC treatments, and clinical characteristics. Results: The study included 1,095 mCRPC patients (320 [29%] White [W], 278 [25%] BAA, 190 [17%] Hispanic [H], 307 [28%] Other races [O]). H had the highest mean age of 69 years, followed by 68 years for O, and 63 years for both W and BAA. Median unadjusted OS was 46.7 months in H, 40.5 months in BAA, 35.3 months in O, and 32.3 months in W. After adjustment, H had significantly lower risk of death vs. W (hazard ratio [95% confidence interval (CI)]: 0.62 [0.42, 0.90]) and BAA had comparable survival to W (0.85 [0.62, 1.16]). BAA had significantly fewer PC-related outpatient (OP) visits vs. W (adjusted incidence rate ratios [IRR] [95% CI]: 0.67 [0.48, 0.93]), but significantly more PC-related emergency room (ER) visits (5.03 [2.03, 12.47]) per patient per year. Race cohorts differed in the proportions of patients treated with novel hormonal therapy (70% W, 63% BAA, 58% H, 67% O) and chemotherapy use (29% BAA, 26% H, 24% W, 19% O). Conclusions: Among Medicaid-insured adult mCRPC patients, H were more likely to live longer than W patients, while BAA and W patients had similar OS. BAA patients had a higher rate of PC-related ER visits but fewer PC-related OP visits as compared to W, showing differential use of PC-related healthcare resources.

26 Background: Racial inequalities in healthcare have long existed in the United States, with Black or African American (BAA) men having higher overall cancer death rates compared to other racial or ethnic groups. One of the greatest disparities is in prostate cancer (PC), which disproportionately affects BAA men, though when matched for stage, whether outcomes differ by race is controversial. This study assessed differences in overall survival (OS) and healthcare resource utilization (HRU) by race in Medicaid-insured patients with metastatic castration-sensitive prostate cancer (mCSPC). Methods: This retrospective longitudinal cohort study evaluated de-identified administrative claims data from the Centers for Medicare and Medicaid Services 100% Medicaid data files, from 01/01/2010 - 12/31/2018. The study included adult patients with a diagnosis for PC, ≥1 claim for androgen deprivation therapy (ADT), diagnosis of metastasis before or within 90 days after ADT, and continuous eligibility for ≥6 months pre-index (defined baseline period) and ≥3 months post-index. The date of first receipt of ADT or first receipt of novel hormonal therapy or docetaxel if initiated within 30 days before ADT defined the index date. OS and HRU were assessed from the index date to the earliest of end of continuous eligibility, data availability, or death. A multivariable Cox proportional hazards model of OS and a multivariable Poisson model of HRU were implemented and controlled for age, plan type, region, median state income, residence in a state with Medicaid expansion, index year, Charlson comorbidity index (CCI), baseline HRU, and clinical characteristics. Results: The study included 1,488 patients with mCSPC (467 [31%] BAA, 446 [30%] White [W], 219 [15%] Hispanic [H], 356 [24%] Other races [O]). H were the oldest (mean age 68 years), followed by O (67 years), W (64 years), and BAA (63 years). BAA and H had the highest CCI (0.6), followed by O (0.5), and W (0.4). Median unadjusted OS was 71.3 months in H, 57.1 months in O, 52.1 months in BAA, and 44.9 months in W. After adjustment, H had significantly lower risk of death compared to W (hazard ratio [95% confidence interval (CI)]: 0.65 [0.43, 0.96]) and BAA patients had comparable survival to W (0.91 [0.69, 1.22]). Adjusted incidence rate ratios (IRR) showed significantly lower incidence of PC-related outpatient (OP) visits for BAA as compared to W (IRR [95% CI]: 0.71 [0.55, 0.99]), per patient per year. The remaining HRU endpoints were not significantly different among racial groups. Conclusions: Among Medicaid-insured adult patients with mCSPC, H were more likely to live longer than W patients. BAA patients had similar survival and lower rates of PC-related OP visits as compared with W, which shows differential use of PC-related healthcare resources between BAA and W.

Single-tablet regimens (STRs) can improve antiretroviral therapy (ART) adherence; however, the relationship between long-term adherence and patient healthcare resource utilization (HRU) is unclear. The objective of this study was to assess long-term ART adherence among people living with HIV (PLHIV) using STRs and multi-tablet regimens (MTRs) and compare HRU over time by adherence.This retrospective study analyzed medical and pharmacy claims (Optum Clinformatics Data Mart Database). Included PLHIV were aged ≥18 years, had ≥1 medical claim with an HIV diagnosis, and had pharmacy claims for a complete STR or MTR. Adherence was analyzed as the proportion of days covered (PDC), stratified as ≥95%, very high; 90-95%, high; 80-90%, moderate;80%, low. Cumulative all-cause and HIV-related HRU were calculated across 4 years. Among PLHIV with ≥4-year follow-up, HRU was assessed by adherence.Among 15,153 PLHIV included, 63% achieved PDC ≥90% during Year 1. Among the subgroup of PLHIV with ≥4-year follow-up (ART adherence showed room for improvement, particularly over the long term. PLHIV receiving STRs exhibited higher adherence vs those receiving MTRs; this difference increased over time. The proportion of PLHIV with higher HRU was significantly higher among those with lower adherence and became greater over time. Interventions and alternative therapies to improve adherence among PLHIV should be explored.

Clinical trials with first- and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) reported severe adverse events (SAEs) in 6%-49% of patients with EGFR-mutated non-small cell lung cancer. This study describes incremental healthcare resource utilization (HRU) and costs associated with real-world management of AEs in this population, with a focus on SAEs.Patients receiving erlotinib, gefitinib, or afatinib as first-line (1L) monotherapy were identified from IQVIA™ Real-World Data Adjudicated Claims-US database (04/01/2012-03/31/2017). Relevant AEs were selected from corresponding prescribing information; SAEs were identified from hospitalization claims. HRU and cost per-patient-per-month (PPPM) were assessed during 1L treatment and compared for patients with and without each AE using multivariate Poisson and linear regression, respectively, adjusting for baseline characteristics.Of 1646 patients, 86.9% were treated with erlotinib, 12.1% with afatinib, and 1.0% with gefitinib. In 1L, 12.2% of patients had ≥1 acute SAE (220.1/1000 patient-years). Patients with any SAE had higher PPPM costs than patients without SAEs (cost difference = $4700, p 0.001). Incremental costs ranged from $2604 PPPM for diarrhea to $10,143 PPPM for microangiopathic hemolytic anemia (MAHA), and were statistically significant for all SAEs (all p 0.001) except MAHA (p 0.0528). Patients with any SAEs had higher rates of HRU relative to patients without SAEs (hospitalization rate ratio = 6.15; outpatient visits rate ratio = 1.21; all p 0.001).More than one-tenth of patients experienced SAEs, resulting in sizeable economic burden with respect to HRU and costs. EGFR-TKIs with more favorable safety profiles may reduce the burden of managing this population.

Background: Mutations in the epidermal growth factor receptor (EGFR) gene have been identified in 10%–50% of patients with non-small cell lung cancer (NSCLC). Exon 20 insertion mutations represent about 2%–10% of this group. Reports of real world experience of NSCLC patients with EGFR exon 20 insertion mutations are limited. This study describes patient characteristics, treatment patterns, and survival outcomes of NSCLC patients with EGFR exon 20 insertions based on real world data. Methods: Flatiron Health electronic health record data, largely from community oncology practices, from January 2011–April 2018 were used for this retrospective observational study. Treatment-naïve (TN) and relapsed/refractory (RR) second-line patients diagnosed with NSCLC with EGFR exon 20 insertion mutation aged ≥18 years at treatment initiation were included. Patient characteristics were described, and Kaplan-Meier analyses were used to assess real world overall survival (rwOS) separately for TN (starting at first-line therapy) and RR (starting at second-line therapy) patients. Results: There were 128 TN and 71 RR patients identified. Median age was 66.5 and 65.0 years for TN and RR patients, respectively, and over half were female (TN: 59.4%, RR: 53.5%). Among 83 TN and 47 RR patients with known ECOG score at advanced diagnosis, most had score 0–1 (TN: 56.3%; RR: 62.0%). Central nervous system metastases were observed in 35.2% of TN and 33.8% of RR patients. While 45.3% of TN patients received any chemotherapy, approximately 20% of both TN and RR patient groups had exposure to various EGFR TKIs. Overall, median rwOS was low at 14.6 months for TN patients, and 10.1 months for RR patients. Conclusion: Real world survival of patients with EGFR exon 20 NSCLC remains poor. Treatment with any chemotherapy regimen was most commonly used followed by EGFR TKIs in TN patients, while the proportion treated with chemotherapy and EGFR TKIs was similar in RR patients. Despite limited evidence in this population, over a fifth of TN and RR patients received EGFR TKI monotherapy. This study demonstrated unmet need for improved therapeutic options in TN and RR patients with NSCLC with EGFR exon 20 insertion mutation.

BackgroundThe NAPOLI-1 trial demonstrated that liposomal irinotecan in combination with fluorouracil (5-FU) and leucovorin (LV) prolonged survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. Real-world data on clinical outcomes associated with liposomal irinotecan in NAPOLI-1-based regimens is needed to further substantiate this.MethodsThis real-world, retrospective chart review study included patients with mPDAC who received NAPOLI-1-based regimens from six academic centers in the United States. Liposomal irinotecan initiation defined the index date. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier methodology.ResultsThere were 374 patients evaluated; median age was 68 years, and 51% were female. Among 326 patients with baseline ECOG information, approximately 74% had ECOG score ConclusionsPatients in a real-world setting treated with NAPOLI-1-based liposomal irinotecan doublet regimens at academic centers were older with poorer performance status compared to trial patients yet had similar outcomes and efficacy. Furthermore, liposomal irinotecan was frequently used in the 3L+ setting where no treatment has been approved and provided clinical benefit.

Conflict, war and the resultant displacement of populations increase risk for infectious disease transmission. Forced migration, loss of safe shelter, loss of livelihood and interrupted access to clean water, electricity and healthcare all lead to increases in epidemic risk. Refugees and displaced people are uniquely vulnerable to COVID-19. The chaos of war and its aftermath override the population health education messages to wear a mask, socially distance and wash hands frequently. Risk of COVID-19 transmission is heightened for people living in densely populated community spaces and overcrowded shelters, particularly for those with inadequate access to clean running water, soap and appropriate sanitation and hygiene facilities. Such circumstances make it challenging to physically distance and maintain proper hand hygiene. Overwhelmed healthcare systems and fragile capacities for social services further contributes to group-specific vulnerabilities of refugees and displaced people. World Health Organization (WHO) and the United Nations High Commissioner for Refugees (UNHCR) have recognised the disproportionate impact of the pandemic on these communities and the need to protect them.1 2 We, the Public Health Working Group for Armenia, echo the call previously made by Kluge et al 3 for an inclusive approach in guiding the global response to the COVID-19 pandemic, emphasising the principle of leaving no one behind. We are particularly concerned about the postconflict setting in the Nagorno-Karabakh Region and the recently displaced Armenian population who have relocated to the Republic of Armenia. In November 2020, the governments of Azerbaijan, Russia and Armenia signed a ceasefire agreement which brought an end to a 6-week long war between Azerbaijan and Armenia over the disputed Nagorno-Karabakh region, an enclave historically populated by indigenous ethnic Armenians (online supplemental file 1). A recent re-escalation of the decades-long conflict, despite the United Nations Secretary General’s call for a global ceasefire during the pandemic4 …

Background Recurrent pericarditis (RP) is characterized by recurrence of symptoms of pericarditis after the original episode has ceased for 4–6 weeks. Though RP is associated with significant morbidity, there is little information regarding the impact of RP on patients' health-related quality of life (HRQOL). Purpose To describe clinical characteristics of and HRQOL burden in patients with RP in the United States. Methods An IRB-approved web-based survey was conducted among patients ≥18 years old with RP who experienced ≥1 recurrence during the prior 12 months. Respondents were recruited from the RHAPSODY clinical trial recruitment database. Patients who met the survey inclusion criteria were asked to provide information on their demographic/clinical characteristics, treatments for RP, and to complete an 11-point pericarditis pain numerical rating scale, the Patient Global Impression of Pericarditis Severity scale, the Patient-Reported Outcomes Measurement Information System® (PROMIS®) Global Health and Sleep Disturbance scales, and questions about the impact of RP on daily life. Results Of the 83 respondents with RP included in the study, 25% responded while experiencing a recurrence. Most respondents were Caucasian (76%) and 55% were female, with mean (standard deviation [SD]) age of 49.3 (13.7) years. Patients frequently reported history of hypertension (39%), anxiety (37%), and depression (34%); 16% and 15% of patients reported having pre-existing autoimmune disease and diabetes, respectively. About half (49%) of patients reported ≥3 recurrences in the prior year, and 40% visited the ER and 25% were hospitalized for their most recent recurrence. Among patients not actively experiencing a recurrence, 37% reported that the duration of their prior episode lasted ≥8 days. Medications most frequently used for RP and pain in the prior year included non-steroidal anti-inflammatory drugs (82%), colchicine (63%), and corticosteroids (29%). Commonly reported symptoms included chest pain (93%), shortness of breath (66%), weakness/fatigue (64%), and heart palpitations (52%). Two-thirds of patients rated the severity of symptoms during the most recent RP episode as moderately severe to very severe, and 48% reported “quite a bit” or “very much” fear of pericarditis recurrence. The mean (SD) value for worst pericarditis pain (0–10 scale) during the recent recurrence was 6.1 (2.3), with 48% reporting severe pain (≥7 on the scale). Patients had substantially worse mean [SD] T scores for PROMIS physical health (37.6 [8.6]), mental health (42.8 [9.9]), and sleep disturbance (60.6 [8.3]) than the general population (50 [10]). Conclusions RP is a burden on the daily lives of patients, resulting in severe pain and impaired quality-of-life including poor physical and mental health, sleep disturbance, and fear of recurrence. This study demonstrates the unmet need for therapies that can rapidly resolve symptoms and prevent recurrences. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Kiniksa Pharmaceuticals Corp.

The extent to which recurrences of pericarditis episodes impact patients’ health-related quality of life (HRQOL) remains poorly understood. This study aimed to evaluate HRQOL and work productivity in patients with recurrent pericarditis (RP). Adult patients from a centralized recruitment database for the rilonacept Phase 2/3 clinical trials were invited to participate in a survey. Inclusion criteria were confirmed RP diagnosis and ≥1 recurrence within the previous 12 months. The 11-Point Pain Numeric Rating Scale, Patient Global Impression of Pericarditis Severity, Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health v1.2, PROMIS Short Form Sleep Disturbance 8b, Work Productivity and Activity Impairment v2.0, and customized questions about fear and economic impact were used. In total, 83 patients (55% female, average age = 49.3 years) completed the survey. The median time since pericarditis diagnosis was 3.0 years at the time of survey completion; 49% experienced ≥3 recurrences in the previous 12 months. Forty percent had an emergency room visit, and 25% were hospitalized for their most recent recurrence. Sixty-six percent of participants rated the symptoms of their last recurrence as severe. The mean value for worst pericarditis pain (0 to 10 scale) during the most recent recurrence was 6.1. The average T-scores for PROMIS physical and mental health were 37.6 and 42.8, respectively, compared with 50 in the general population. Participants reported 50% of overall work impairment and 62% of activity impairment due to RP. In conclusion, patients with RP experienced a high number of recurrences with severe symptoms that substantially reduced their HRQOL and work productivity.

Introduction: Real-world data describing acute pericarditis (AP) etiology in the US are limited. Data on the characteristics of recurrent pericarditis (RP) patients (pts) are also sparse. To fill this gap, our study assesses longitudinal data from a nationwide privately-insured population. Methods: OptumHealth Reporting and Insights employer claims data (1/2007-3/2017) were used. AP pts were identified and categorized as idiopathic or non-idiopathic etiology based on presence or absence of attributable conditions. Among idiopathic AP pts, a subgroup of RP pts was identified. Recurrence was defined as ≥2 AP events separated by >4 weeks. First recurrence date marked the index date. Pts aged ≥18 years with ≥12 months of continuous enrollment pre-index (baseline) were included. Results: Of 17,168 AP pts, 4,175 (24.3%) had non-idiopathic and 12,993 (75.7%) had idiopathic etiology (Table 1). Application of inclusion criteria left 8,822 idiopathic AP pts, of whom 1,604 (18.2%) had ≥1 recurrence during a mean observation period of 29 months. On average, idiopathic RP pts were aged 50.7 years, 51.6% female, and 42.3% had baseline history of hypertension, 23.8% of coronary artery disease, 11.7% of hypercholesterolemia, and 7.3% of myocardial infarction. Mean (±SD) time from initial AP diagnosis to first recurrence was 8.7 (±12.1) months and mean (±SD) number of recurrences was 1.7 (±1.3) per pt. In idiopathic RP pts with ≥4 years of follow-up after the initial AP diagnosis (N=512), 35.9% had ≥2, 18.2% had ≥3, and 9.8% had ≥4 recurrences within 4 years. Conclusions: The etiologic distribution and proportion of pts with RP are consistent with previous reports. About 36% of RP pts experience ≥2 recurrences after AP diagnosis over 4 years. RP represents a significant clinical burden for affected pts.

Background: Up to 30% of incident pericarditis patients (pts) recur within 18 months. Recurrences can be debilitating and typically last several weeks despite conventional treatments (Tx). Recurrence burden (likelihood and frequency) is poorly defined. Improved understanding of recurrence burden can inform Tx decisions and the introduction of novel therapies. Method: Adults with idiopathic recurrent pericarditis (RP) were identified in the OptumHealth Reporting and Insights dataset (2007-2017). RP was defined as ≥2 episodes separated by >4 weeks. Disease duration (time from first episode to end of last recurrence, confirmed by a 1.5-year recurrence-free period) was evaluated using Kaplan-Meier analysis. Recurrence frequency and time between recurrences were evaluated among pts with 4+ years of observation. Result: Of the 1,604 RP pts, mean age was 50.7 years and 51.6% were female. Median RP duration was 2.1 and 3.1 years for pts with ≥1 and ≥2 recurrences, respectively ( Figure ). Over 4 years with RP, 15% of pts with ≥1 recurrence and 22% of pts with ≥2 recurrences had more than one episode/year. Mean ± SD time from first episode to first recurrence was 14.5 ± 17.9 months and 10.7 ± 12.1 months between subsequent recurrences. Conclusion: Recurrent pericarditis can span many years. Over half of pts with ≥2 recurrences have RP persisting over 3 years. Subsequent recurrences are more frequent but highly variable, making RP unpredictable. Tx to reduce recurrences could benefit pts with ≥2 recurrences.

Introduction: Patients with relapsed/refractory multiple myeloma (RRMM) resistant to multiple drug classes remain a high unmet need population, despite advances in MM patient care. The objective of this study was to assess real-world treatment patterns and outcomes in patients with RRMM who had failed multiple prior lines of therapy (LOT) and were refractory to multiple drug classes to identify gaps in their treatment pathways. Methods: This longitudinal retrospective cohort study utilized the COTA de-identified real-world database derived from US electronic health records of partnered healthcare providers from Q3 1988 through Q1 2020. Adults with active RRMM previously exposed to a proteasome inhibitor (PI) and an immunomodulatory drug and who received ≥3 prior LOTs were identified. Patients were further categorized as refractory to a PI and an immunomodulatory drug (double-class refractory [DCR]) or additionally to an anti-CD38 monoclonal antibody (i.e. daratumumab; triple-class refractory [TCR]). Determining refractory status was based on International Myeloma Working Group criteria. Index LOT was a new LOT after evidence of DCR or TCR status following ≥3 (DCR) or ≥4 (TCR) prior LOTs. Patient characteristics described included Eastern Cooperative Oncology Group (ECOG) performance status, International Staging System (ISS) stage, cytogenetic risk, age, index date, sex, and follow up time. Treatment pattern assessments included treatments received before/during/after index LOT, reasons for discontinuation, refractory status, and retreatment characteristics. Patient outcomes (overall survival [OS], duration of treatment [DOT], and time to next therapy [TTNT]) were analyzed using Kaplan-Meier survival analysis methods. Results: After excluding patients who were aged 62%), and 14-16% had ISS stage III. Patients had a median of 3 (DCR) and 6 (TCR) prior LOTs. Prior to index LOT, bortezomib and lenalidomide were the most commonly received PI and immunomodulatory drug (received by >98% of DCR or TCR patients) and the most common PI and immunomodulatory drugs to which patients were refractory (71% and 84% DCR; 76% and 83% TCR, respectively). At index LOT, PI/immunomodulatory drug-based and daratumumab-based therapies remained the most common therapies. Bortezomib and lenalidomide had the longest time to refractory status and highest retreatment rates among DCR or TCR patients. Approximately 40% of TCR patients were retreated with daratumumab-based therapies after becoming refractory (Table). After index LOT, 70% of DCR and 58% of TCR patients continued to a subsequent LOT. Patients most frequently discontinued index LOT due to disease progression (59% DCR; 60% TCR), toxicity (23% DCR; 25% TCR), or doctor preference (14% DCR; 10% TCR). Median duration of gaps between LOTs generally were shorter than 1 month (Table). Median OS was 22.3 (DCR) and 11.6 (TCR) months. Median DOT was 3.3 (DCR) and 2.8 (TCR) months, and median TTNT was 4.1 (DCR) and 3.2 (TCR) months. In multivariate statistical analyses, inferior baseline ECOG performance scores, and high-risk cytogenetic abnormalities were associated with worse prognosis (higher risk of death, shorter DOT, and shorter TTNT) in DCR and TCR patients. Age was not a significant factor after adjusting for other baseline factors. Conclusions: Treatment options are limited for US patients with DCR and TCR RRMM. DCR and TCR patients were frequently retreated with a PI, an immunomodulatory drug, or daratumumab, despite refractoriness to these agents. Many DCR and TCR MM patients stopped active MM treatment after discontinuing index treatment. Patients with DCR and TCR MM have poor prognosis, especially among high cytogenetic risk and poor performance status patients. This study provides the benchmark for new therapies, like BCMA-targeted agents, to be tested in this population. Funding: GSK (Study 217353). Figure 1 Figure 1. Disclosures Wang: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gorsh: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. DerSarkissian: Analysis Group, Inc.: Current Employment. Paka: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Bhak: Analysis Group, Inc.: Current Employment; GlaxoSmithKline: Research Funding. Boytsov: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Zichlin: GlaxoSmithKline: Research Funding; Analysis Group, Inc.: Consultancy, Current Employment. Sansbury: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Yee: Analysis Group, Inc.: Current Employment; GlaxoSmithKline: Research Funding. Ferrante: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Khanal: GlaxoSmithKline: Research Funding; Analysis Group, Inc.: Current Employment. Noman: Analysis Group, Inc.: Current Employment; GlaxoSmithKline: Research Funding. Duh: Novartis: Other: I am an employee of Analysis Group, a consulting company that received funding from Novartis for this research study..

Introduction Guidelines recommend chemoimmunotherapy and novel agents such as Bruton's tyrosine kinase inhibitors and B-cell lymphoma 2 inhibitors for the treatment of CLL. AE profiles differ across therapies, and management of AEs in patients with CLL treated with novel agents incurs burden on healthcare professionals (HCPs) and oncology practices. Time and personnel costs associated with AE management are not well understood for patients with CLL and are overlooked while assessing the value of oncology drugs. To assess practice burden, this study quantified HCP time and personnel costs related to AE management for patients with CLL who received a novel agent, either acalabrutinib, ibrutinib, or venetoclax. Methods HCPs (i.e., oncologists, pharmacists, physician assistants, nurse practitioners, and registered nurses) who actively treated ≥5 patients with CLL during the past year with >1 patient receiving acalabrutinib, ibrutinib, or venetoclax in the past month were recruited through a physician panel vendor to participate in a longitudinal, observational, prospective survey. This study was conducted in two phases (November 2020-January 2021; April-June 2021). Over the 2-month data collection period, HCPs reported on a daily basis the time spent performing AE management activities for CLL patients receiving a novel agent, which included 1) interactions with patients in-person or via remote consultation (telephone, video, or email), 2) interactions with other HCPs, and 3) other management activities that did not include interactions with patients or other HCPs (e.g., recording notes in patient's charts, ordering lab tests). Mean time and personnel costs per AE management activity were summarized using descriptive statistics. Personnel costs (USD) were calculated by multiplying median wage information reported by the ureau of Labor Statistics Occupational Employment Statistics survey by HCP-reported time spent managing AEs. Results Among 49 HCPs enrolled in the survey, 36 (73%; Table 1) reported managing ≥1 AE during a total of 1,106 AE management activities (229 for acalabrutinib; 500 for ibrutinib; 377 for venetoclax) for 421 patients with CLL during the 2-month study period. Among all patients, 108 (26%), 186 (44%), and 129 (31%) received acalabrutinib, ibrutinib, or venetoclax in any line, respectively (Table 2). Anemia was the most frequently managed AE reported among all patients (19%), but differed by treatment: 11%, 19%, and 26% for patients treated with acalabrutinib, ibrutinib, and venetoclax, respectively (Table 2). Other AEs reported among ≥10% of patients with a reported AE management activity also differed by treatment. For acalabrutinib, this included only headache. For both ibrutinib and venetoclax patients, thrombocytopenia, diarrhea, and myalgia were managed in ≥10% of patients. For venetoclax patients, back pain and arthralgia were also managed in ≥10% of patients. Mean (standard deviation [SD]) time spent managing AEs per activity was 11.8 (7.7) minutes (min) overall, 12.1 (7.4) min for acalabrutinib, 11.6 (6.9) min for ibrutinib, and 11.8 (8.9) min for venetoclax (Table 3). Mean time per AE management activity was numerically similar across the three treatments overall and stratified by type of HCP, treatment duration, and line of therapy. We noted differences in the type of HCP managing AEs by treatment, with a lower proportion of oncologists managing acalabrutinib AEs compared to the other two therapies. Corresponding mean (SD) personnel costs per AE management activity were $16.0 ($10.6) overall, and $14.4 ($9.8) for acalabrutinib, $16.3 ($9.8) for ibrutinib, and $16.7 ($11.9) for venetoclax. Conclusions This study demonstrates the importance of accounting for time and labor costs related to AE management, as results suggest that the burden to HCPs related to AE management for patients with CLL treated with acalabrutinib, ibrutinib, and venetoclax is substantial. During the 2-month study period, almost three-quarters of HCPs reported managing ≥1 AEs and an average of 12 AE management days was observed across these HCPs. While mean time and personnel costs were similar, differences in types of AE and types of HCPs managing AEs were observed across treatments. Future research should confirm our observed differences in types of AE and types of HCPs managing AEs by treatment to comprehensively assess the burden of managing AEs for patients with CLL. Figure 1 Figure 1. Disclosures Wahlstrom: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. DerSarkissian: Analysis Group, Inc.: Current Employment. Kunzweiler: Apellis: Other: Employee of Analysis Group, Inc., Research Funding. Castriota: Analysis Group, Inc.: Ended employment in the past 24 months. Chang: Analysis Group, Inc.: Current Employment. Cheung: Analysis Group, Inc.: Ended employment in the past 24 months. Gu: Analysis Group, Inc.: Current Employment. Guo: Analysis Group, Inc.: Current Employment. Duh: Novartis: Other: I am an employee of Analysis Group, a consulting company that received funding from Novartis for this research study.. Ryan: AstraZeneca: Current Employment, Current equity holder in publicly-traded company.

Context Real-world data on treatment patterns and outcomes in patients with RRMM resistant to multiple drug classes are limited. Objective To assess clinical treatment patterns and refractory status in patients with RRMM. Methods This longitudinal retrospective cohort study utilized the COTA de-identified real-world database derived from US electronic medical records of partnered healthcare providers from Q3 1988 through Q1 2020; 650 adults with active RRMM previously exposed to ≥1 proteasome inhibitor (PI) and 1 immunomodulatory drug (double-exposed) and who received ≥3 prior lines of therapy (LOTs) were identified. Patients were further categorized as refractory to a PI and an immunomodulatory drug (double-class refractory [DCR]; n=381) or additionally to an anti-CD38 monoclonal antibody (i.e., daratumumab; triple-class refractory [TCR]; n=173). Index LOT was the fourth (double-exposed) or new LOT after evidence of DCR or TCR status following ≥3 or ≥4 prior LOTs (DCR or TCR, respectively). Median follow-ups from index LOT initiation through end of data availability/death were 24 (double-exposed), 14 (DCR), and 8 (TCR) months. Assessments included therapies received before/during the index LOT, duration of treatment (DOT), and treatment discontinuation reasons. Results Patient characteristics included age ≥65 years (49% DCR; 53% TCR), International Staging System stage III (14%; 16%), and high-risk cytogenetics (56%; 66%); >62% had prior autologous stem cell transplantation. Patients had a median of 3 (DCR) and 6 (TCR) prior LOTs. Retreatment percentages among DCR patients were 60% (PI) and 69% (immunomodulatory drug); 30% were exposed to daratumumab. For TCR patients, retreatment percentages were 65% (PI), 60% (immunomodulatory drug), and 29% (daratumumab). Median DOTs were 3.3 (DCR) and 2.8 months (TCR). Patients discontinued index therapy most commonly due to disease progression (59% DCR; 60% TCR) or toxicity (23%; 24%). After index LOT, 70% DCR and 58% TCR patients continued to a subsequent LOT. Conclusions Treatment options are limited for US patients with heavily pretreated RRMM. DCR/TCR patients were frequently retreated with a PI, immunomodulatory drugs, or daratumumab (TCR patients) despite refractoriness to these agents. Many DCR/TCR patients stopped active MM treatment after discontinuing index treatment. Funding GlaxoSmithKline (212953).

BACKGROUND Effective treatment options for patients with chronic myeloid leukemia (CML) or Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) who have the threonine to isoleucine mutation at codon 315 (T315I) are few. The objective of this study was to compare overall survival (OS) between patients with CML and those with Ph+ ALL who received treatment with ponatinib versus allogeneic stem cell transplantation (allo-SCT). METHODS A post hoc, retrospective, indirect comparison of OS among patients who received single-agent ponatinib in the Ponatinib Ph+ ALL and CML Evaluation (PACE) trial with those who underwent allo-SCT as reported to the European Bone Marrow Transplant registry, stratified by CML disease phase and Ph+ ALL, was conducted. Kaplan-Meier survival curves and multivariate Cox proportional-hazards models were used to compare OS between intervention groups, adjusting for time from diagnosis to intervention, age, sex, and geographic region; 24-month and 48-month OS rates and median OS were reported. RESULTS After adjustment for potential confounders, 24-month and 48-month OS rates were significantly higher in patients with chronic-phase CML (CP-CML) who received ponatinib compared with those who underwent allo-SCT (24 months: 84% vs 60.5%, respectively; P = .004; 48 months: 72.7% vs 55.8%, respectively; P = .013), with a hazard ratio (HR) of 0.37 (95% confidence interval [CI], 0.16-0.84; P = .017). In patients who had accelerated-phase CML, OS rates were not significantly different between the groups (HR, 0.90; 95% CI, 0.20-4.10; P = .889). In patients who had blast-crisis CML and those with Ph+ ALL, ponatinib was associated with shorter OS compared with allo-SCT (blast-crisis CML: HR, 2.29 [95% CI, 1.08-4.82; P = .030]; Ph+ ALL: HR, 2.77 [95% CI, 0.73-10.56; P = .146]). CONCLUSIONS Although allo-SCT remains an important treatment option for patients with T315I-positive advanced CML and Ph+ ALL, ponatinib represents a valuable alternative for patients with T315I-positive CP-CML. Cancer 2017;123:2875–80. © 2017 American Cancer Society.

Characterize patterns of weight change among subjects with obesity.A retrospective observational longitudinal study of subjects with obesity was conducted using the General Electric Centricity electronic medical record database. Subjects who were ≥18 years old with BMI ≥30 kg/mA total of 177,743 subjects were included: 85.1% of subjects were in the stable weight, 9.3% in the modest, 2.3% in the moderate, and 3.3% in the high weight loss groups. The proportion of subjects who maintained or continued to lose weight decreased over the 2 year observation period; 11% of those with high weight loss continued to lose weight and 19% maintained their weight loss. This group had the lowest percentage of subjects who regained ≥50% of lost weight and the lowest proportion of subjects with weight cycling (defined as not continuously losing, gaining, or maintaining weight throughout the 2 year observation period relative to its beginning). This trend persisted in subgroups with class II-III obesity, pre-diabetes, and type 2 diabetes.Weight cycling and regain were commonly observed. Subjects losing the most weight during the initial period were more likely to continue losing weight.